Science Book a Day Interviews John Quackenbush

John Quackenbush received his PhD in 1990 in theoretical physics from UCLA working on string theory models. Following two years as a postdoctoral fellow in physics, Dr. Quackenbush applied for and received a Special Emphasis Research Career Award from the National Center for Human Genome Research to work on the Human Genome Project. He spent two years at the Salk Institute and two years at Stanford University working at the interface of genomics and computational biology. In 1997 he joined the faculty of The Institute for Genomic Research (TIGR) where his focus began to shift to understanding what was encoded within the human genome. – From SELECTBIO

The truth is that I approached by the publisher who was exploring creating a series of books on scientific topics that were written to appeal to “the cocktail party crowd.” What he meant that he was looking for books that presented scientific topics in a format that was clearly written and easy to read, but which didn’t talk down to the audience. He had heard that I was good at explaining science to a general audience and so he asked me to contribute one of the first two volumes. (The other was on global warming. The publishing company was bought while the books were being printed and the series never went beyond the first two books.)

I agreed because I was involved in the Human Genome Project from its early days and I thought the story of its genesis as well as the science that both drove the project and emerged from it were compelling. I also thought it was important to educate people about the promise and limitations of genomics because it was clear that it was poised to become an extremely important part of our everyday lives. And while writing the book consumed a lot of weekend afternoons and otherwise spare evenings, pulling together the story was fun.

#2 – You previously worked in physics before starting to work in biology. What are the similarities that allowed you to make such a transition?

While I’ve certainly applied some of the basic physics I learned as an undergraduate, nothing I did during my PhD has had any relevance to anything I’ve done since transitioning to a career in genomics. But what physics taught me to think and solve problems–and that is, fundamentally, what any good education should do. I think physics training does a very good job of teaching people to take complex problems, to reduce them to simpler problems we can understand, and then integrating what we’ve learned to gain insight into the initial problem. Some of the most interesting work I’ve done over the years has been based on drawing analogies to concepts in physics. For example, we’ve developed a new approach to modeling how biological systems transition from one state to another by drawing an analogy to quantum mechanical state transitions.

#3 – In your book you caution against over-estimating the power of genomics. How do you think we are overestimating it?

I think people tend to believe that genetics plays a far greater role in determining who we are than it really does. But I think a big part of the reason is that we’re first introduced to genetics through a discussion of Mendel and his peas–where the presence or absence or a particular gene variant is described as being an absolute determinant of a particular trait. And so people seem to think that all traits are what we’d call highly penetrant Mendelian traits. But the situation is much more complex. Nearly every phenotypic trait we can imagine reflects that combined effects of three elements: genes, environment, and chance. And even the genes play a complex role in which most traits are polygenic meaning that they are influenced by the interplay of many genes. So rather than determining who we are, our genes interact together in complex ways and play a role with other factors in influencing who we are,

So whether or not you have genes that increase your risk for lung cancer or obesity, whether you smoke or how much you eat are going to play a major role in seeing whether these genetic factors play themselves out.

#4 – Who did you write your book for? Academics? Students? Teachers? What has the response to the book been?

The book was written for an intelligent lay audience. My acid test for what I was writing was asking myself whether each chapter “passed the mom test.” Could my mother, who isn’t a scientist, understand it? The book was published in 2011 and the response has been quite good. The reviews on Amazon are very good and I think the overall rating is 4.3 stars, which isn’t bad. And if you ask my mother, she’ll tell you that the book should be a 5-star publication.

#5 – Are you working on any new projects/books that you can tell us about?

I would love to write another mass-market book, but I haven’t actively pursued finding a publisher. I would also love to update the book to address a few little things that crept in during writing and editing–but also to update the book to reflect some of the exciting science that has happened in the intervening years.

My research work has taken off in exciting directions. I do computational and systems biology and my colleagues and I have new ways of modeling gene regulatory networks that are leading to new insights into disease, including differences between men and women in the development and progression of disease. We’ve also developed an entirely new approach to looking at the relationship between genetic variants and gene expression that naturally explains a great deal of what we understanding about genetics. And there is much more that we’re doing. The reason I got into science is that it was fun–and the reason I am still passionate about doing it is that it’s about the best job I can imagine.